Long-term effects of neonatal basal forebrain cholinergic lesions on radial maze learning and impulsivity in rats

Behav Pharmacol. 2006 Sep;17(5-6):517-24. doi: 10.1097/00008877-200609000-00018.

Abstract

We examined long-term behavioural effects of neonatal lesions of the cholinergic basal forebrain obtained by intracerebroventricular injections of 192 IgG saporin (192 IgG-Sap). Five-month-old Wistar male rats (injected with 192 IgG-Sap or phosphate-buffered saline on postnatal day 7) were tested using operant chambers with two nose-poking holes, delivering one food pellet immediately or five pellets after a delay. The length of delay progressively increased over days (from 0 to 100 s). When compared with controls, 192 IgG-Sap rats showed a slight preference for smaller immediate over larger delayed rewards, thus indicating elevated intolerance to delay (i.e. more impulsivity). Sibling animals were tested in a computerized radial maze (baited vs. nonbaited arm procedure). 192 IgG-Sap rats appeared slower than controls in accomplishing the task. The neonatal 192 IgG-Sap lesion did not alter cortical levels of serotonin and/or its metabolites, but induced a marked cortical cholinergic loss. Our data suggest that a prolonged basal forebrain cholinergic hypofunction produces (i) an impairment in cognitive performances that is detectable only when highly complex tasks are used; (ii) a slight enhancement of the impulsive behavioural profile. This animal model may thus be useful to investigate some cognitive deficits and other secondary symptoms seen in Alzheimer's disease.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / chemically induced
  • Alzheimer Disease / physiopathology
  • Animals
  • Animals, Newborn
  • Antibodies, Monoclonal
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / physiopathology*
  • Choline O-Acetyltransferase / metabolism
  • Cholinergic Agents
  • Cholinergic Fibers / drug effects
  • Cholinergic Fibers / physiology*
  • Disease Models, Animal
  • Female
  • Hippocampus / drug effects
  • Hippocampus / physiopathology
  • Immunotoxins
  • Impulsive Behavior / chemically induced
  • Impulsive Behavior / physiopathology*
  • Injections, Intraventricular
  • Male
  • Maze Learning / drug effects
  • Maze Learning / physiology*
  • N-Glycosyl Hydrolases
  • Rats
  • Rats, Wistar
  • Reaction Time / drug effects
  • Reaction Time / physiology
  • Ribosome Inactivating Proteins, Type 1
  • Saporins
  • Serotonin / metabolism

Substances

  • 192 IgG-saporin
  • Antibodies, Monoclonal
  • Cholinergic Agents
  • Immunotoxins
  • Ribosome Inactivating Proteins, Type 1
  • Serotonin
  • Choline O-Acetyltransferase
  • N-Glycosyl Hydrolases
  • Saporins